Pharmacol Res 2022 Jun 27:106329. Epub 2022 Jun 27.
Cell & Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, Australia 2050; Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia 2050; Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, Australia 2050; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, Australia 2050. Electronic address:
Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in haematological malignancies. Unfortunately, this success has not been replicated in solid tumours, with only a small fraction of patients achieving complete responses. A number of obstacles to effective CAR-T cell therapy in solid tumors have been identified including tumor antigen heterogeneity, poor T cell fitness and persistence, inefficient trafficking and inability to penetrate into the tumor, immune-related adverse events due to on-target/off-tumor toxicity, and the immunosuppressive tumor microenvironment. Read More